Hepcidin as a key regulator of iron homeostasis triggers inflammatory features in the normal endometrium

Yuko Izumi, Izumi, Yuko, Hisashi Kataoka, Akemi Koshiba, Koshiba A, Ito F, Fumitake Ito, Yukiko Tanaka, Tanaka Y, Osamu Takaoka, Takaoka O, Eiko Maeda, Maeda E, Hiroyuki Okimura, Okimura H, Takuya Sugahara, Sugahara T, Yosuke Tarumi, Koki Shimura, Shimura K, Khaleque N Khan, Khaleque Newaz Khan, Khan KN, Kusuki I, Izumi Kusuki, Taisuke Mori, Mori T
Free radical biology & medicine · 2023 · vol. 209(Pt 2) , pp. 191–201 · doi:10.1016/j.freeradbiomed.2023.10.402 · PMID:37884101 · W3176668179
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This study found that increased hepcidin in menstrual blood from women with endometriosis leads to iron accumulation, oxidative stress, and inflammation in normal endometrial cells.

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Abstract

Menstrual blood, containing high iron levels, can undergo retrograde transport into the abdominal cavity. Excess iron causes oxidative stress and inflammation. Iron metabolism is regulated by hepcidin, and serum hepcidin levels are increased in patients with endometriosis; however, the functions of hepcidin in normal endometrium remain unclear. We therefore aimed to examine hepcidin concentrations in patients with endometriosis and to determine if iron accumulation and hepcidin increased the production of reactive oxygen species (ROS) and inflammation in normal endometrial cells. We determined hepcidin levels in peritoneal fluid and menstrual blood from patients with and without endometriosis (25/16 and 15/15 patients, respectively). We also examined the effects of hepcidin on ferroportin expression, iron accumulation, and ROS generation in normal endometrial stromal cells (NESCs) from 20 women who underwent surgery for uterine leiomyoma, using immunohistochemistry and immunofluorescence analyses and analyzed its effect on the expression of inflammatory cytokines by real-time polymerase chain reaction. There was no significant difference in iron concentrations in menstrual blood or peritoneal fluid between women with and without endometriosis; however, women with endometriosis had significantly higher hepcidin levels in menstrual blood. Hepcidin reduced the expression of ferroportin in NESCs and promoted the accumulation of ferrous iron. Hepcidin plus ferrous iron increased the production of ROS and inflammatory cytokines compared with ferrous iron alone. These results indicate that women with endometriosis have high hepcidin levels in menstrual blood, leading to increased iron production, oxidative stress, and inflammation, which may, in turn, promote the development of endometriosis.

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Condition tags

endometriosis

MeSH descriptors

Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis

Citation neighborhood (2-hop)

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. Outer rings show 2-hop neighbours — papers reached through the immediate citers/citees. [ collapse to 1-hop ]

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